Glycosaminoglycan synthesis in fibroblasts (Homo sapiens)

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1-11CSGALNACT2HS3ST1CHST12chondroitin-[core protein]HS6ST3CHSY1CHST15EXTL13-O-(β-D-xylosyl)-L-seryl-[protein]CHST11UDP-N-acetyl-α-D-galactosaminedermatan-[core protein]CHPF2Heparan-sulfate-3-N-disulfate4-β-D-galactosyl-O-β-D-xylosyl-[protein]HS6ST1Dermatan-NAcGal-4-sulfatesEXTL2HS3ST1EXT23-β-D-galactosyl-4-β-D-galactosyl-O-β-D-xylosyl-[protein]GLCEHS6ST2B4GALT7heparin-glucosamine-3-O-sulfateEXTL3HS3ST3A1USTCHST1CHST13XYLT2GalNAc-GlcA-GalNAc-GlcA-Gal-Gal-Xyl-PrB3GAT3XYLT1CHST7GlcA-GalNAc-GlcA-Gal-Gal-Xyl-Proteinsdeacetylated heparosan-[core protein]GlcA-GlcNAc-GlcA-Gal-Gal-Xyl-ProteinNDST4[heparan sulfate] containing GlcNSchondroitin 4'-sulfateNDST2NDST13-β-D-glucosyluronate-3-β-D-galactosyl-4-β-D-galactosyl-O-β-D-xylosyl-[protein]CSGALNACT1HS2ST1B3GAT1CHPFHS3ST2NDST3[heparosan]-containing α-L-iduronateCHST143-β-D-glucosyluronate-3-β-D-galactosyl-4-β-D-galactosyl-O-β-D-xylosyl-[protein]HS3ST3B1DSECHST3GalNAc-GlcA-Gal-Gal-Xyl-ProteinsCHSY3Heparan-sulfate-L-IdoA-2SB3GALT6EXT1GlcNAc-GlcA-GlcNAc-GlcA-Gal-Gal-Xyl-Coreheparosan-[core protein]chondroitin 6'-sulfateB3GAT2UDP-α-D-xyloseUDP-α-D-galactoseUDP-α-D-galactoseUDP-α-D-glucuronateNDST4NDST3NDST1NDST2EXT2EXT1Heparan-GlcN-6-N-bisulfateHeparan-Glc-N-3-6-trisulfateDermatan-SulfateDermatan-sulfate-L-IdoA2SDermatan-NAcGal-46-disulfatesCSGALNACT1CSGALNACT2CHSY3CHPFCHSY1


Description

Glycosaminoglycans (GAGs) are key components of the extracellular matrix secreted by fibroblasts. This pathway shows the metabolic reactions necessary to synthesize three types of GAGs, namely chondroitin sulfate, dermatan sulfate and heparan sulfate. The synthesis takes place in the Golgi apparatus and begins with UDP-α-D-xylose. After this molecule is converted to 3-β-D-glucosyluronate-3-β-D-galactosyl-4-β-D-galactosyl-O-β-D-xylosyl-[protein] via three metabolic reactions, the pathway separates into two branches. One of them leads to the synthesis of chondroitin sulfate and dermatan (di)sulfate, while the other ends with heparan mono-, bi- or trisulfate. Some of the reactions are catalyzed by unknown enzymes that should be researched in the future.

This pathway was created based on the information from the pathways found in MetaCyc and HumanCyc databases (see Bibliography). As some of the metabolites do not have identifiers in databases supported by PathVisio (such as ChEBI or KEGG), their MetaNetX IDs were added in the comments.

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Bibliography

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  1. Caspi R, Billington R, Keseler IM, Kothari A, Krummenacker M, Midford PE, Ong WK, Paley S, Subhraveti P, Karp PD; ''The MetaCyc database of metabolic pathways and enzymes - a 2019 update.''; Nucleic Acids Res, 2020 PubMed Europe PMC Scholia
  2. Huang YF, Mizumoto S, Fujita M; ''Novel Insight Into Glycosaminoglycan Biosynthesis Based on Gene Expression Profiles.''; Front Cell Dev Biol, 2021 PubMed Europe PMC Scholia
  3. Casale J, Crane JS; ''Biochemistry, Glycosaminoglycans''; https://www.ncbi.nlm.nih.gov/books/NBK544295/#:~:text=The%20process%20of%20GAG%20biosynthesis,and%20UDP%2DN%2Dacetylgalactosamine., 2023
  4. Basu A, Patel NG, Nicholson ED, Weiss RJ; ''Spatiotemporal diversity and regulation of glycosaminoglycans in cell homeostasis and human disease.''; Am J Physiol Cell Physiol, 2022 PubMed Europe PMC Scholia
  5. Karp PD, Billington R, Caspi R, Fulcher CA, Latendresse M, Kothari A, Keseler IM, Krummenacker M, Midford PE, Ong Q, Ong WK, Paley SM, Subhraveti P; ''The BioCyc collection of microbial genomes and metabolic pathways.''; Brief Bioinform, 2019 PubMed Europe PMC Scholia
  6. Caspi R; ''Pathway: glycosaminoglycan-protein linkage region biosynthesis''; https://metacyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-6557, 2010
  7. Caspi R; ''Pathway: chondroitin sulfate biosynthesis''; https://metacyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-6567&detail-level=2, 2010
  8. Caspi R; ''Pathway: heparan sulfate biosynthesis''; https://metacyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-6558&detail-level=2, 2010
  9. Caspi R; ''Pathway: superpathway of heparan sulfate biosynthesis''; https://metacyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-6564&detail-level=2, 2010
  10. Caspi R; ''Pathway: dermatan sulfate biosynthesis''; , 2010
  11. Caspi R; ''Pathway: chondroitin biosynthesis''; https://biocyc.org/HUMAN/NEW-IMAGE?type=PATHWAY&object=PWY-6566, 2010

History

CompareRevisionActionTimeUserComment
126912view19:34, 2 July 2023JuliabladOntology Term : 'fibroblast' added !
126911view19:34, 2 July 2023JuliabladOntology Term : 'classic metabolic pathway' added !
126910view19:32, 2 July 2023JuliabladNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
3-O-(β-D-xylosyl)-L-seryl-[protein]MetaboliteC02399 (KEGG Compound)
3-β-D-galactosyl-4-β-D-galactosyl -O-β-D-xylosyl-[protein]MetaboliteC04825 (KEGG Compound)
3-β-D-glucosyluronate-3-β-D-galactosyl -4-β-D-galactosyl-O-β-D-xylosyl-[protein]Metabolite80007 (ChEBI)
3-β-D-glucosyluronate-3-β-D-galactosyl -4-β-D-galactosyl-O-β-D-xylosyl-[protein]MetaboliteC04903 (KEGG Compound)
4-β-D-galactosyl-O-β-D-xylosyl-[protein]Metabolite25245405 (PubChem-compound)
B3GALT6GeneProductENSG00000176022 (Ensembl)
B3GAT1GeneProductENSG00000109956 (Ensembl)
B3GAT2GeneProductENSG00000112309 (Ensembl)
B3GAT3GeneProductENSG00000149541 (Ensembl)
B4GALT7GeneProductENSG00000027847 (Ensembl)
CHPF2GeneProductENSG00000033100 (Ensembl)
CHPFGeneProductENSG00000123989 (Ensembl)
CHST11GeneProductENSG00000171310 (Ensembl)
CHST12GeneProductENSG00000136213 (Ensembl)
CHST13GeneProductENSG00000180767 (Ensembl)
CHST14GeneProductENSG00000169105 (Ensembl)
CHST15GeneProductENSG00000182022 (Ensembl)
CHST1GeneProductENSG00000175264 (Ensembl)
CHST3GeneProductENSG00000122863 (Ensembl)
CHST7GeneProductENSG00000147119 (Ensembl)
CHSY1GeneProductENSG00000131873 (Ensembl)
CHSY3GeneProductENSG00000198108 (Ensembl)
CSGALNACT1GeneProductENSG00000147408 (Ensembl)
CSGALNACT2GeneProductENSG00000169826 (Ensembl)
DSEGeneProductENSG00000111817 (Ensembl)
Dermatan-NAcGal-4-sulfatesMetaboliteMetaNetX: MXNM96191
Dermatan-NAcGal-46-disulfates MetaboliteMetaNetX: MXNM96257
Dermatan-SulfateMetabolite18376 (ChEBI)
Dermatan-sulfate-L-IdoA2SMetaboliteMetaNetX: MNXM7277
EXT1GeneProductENSG00000182197 (Ensembl)
EXT2GeneProductENSG00000151348 (Ensembl)
EXTL1GeneProductENSG00000158008 (Ensembl)
EXTL2GeneProductENSG00000162694 (Ensembl)
EXTL3GeneProductENSG00000012232 (Ensembl)
GLCEGeneProductENSG00000138604 (Ensembl)
GalNAc-GlcA-Gal-Gal-Xyl-ProteinsMetaboliteMetaNetX: MXNM18007
GalNAc-GlcA-GalNAc- GlcA-Gal-Gal-Xyl-PrMetaboliteMetaNetX: MXNM148368
GlcA-GalNAc-GlcA-Gal-Gal-Xyl-ProteinsMetaboliteMetaNetX: MXNM148183
GlcA-GlcNAc-GlcA-Gal-Gal-Xyl-Protein MetaboliteMetaNetX: MNXM148103
GlcNAc-GlcA-GlcNAc-GlcA -Gal-Gal-Xyl-CoreMetaboliteMetaNetX: MNXM148048
HS2ST1GeneProductENSG00000153936 (Ensembl)
HS3ST1GeneProductENSG00000002587 (Ensembl)
HS3ST2GeneProductENSG00000122254 (Ensembl)
HS3ST3A1GeneProductENSG00000153976 (Ensembl)
HS3ST3B1GeneProductENSG00000125430 (Ensembl)
HS6ST1GeneProductENSG00000136720 (Ensembl)
HS6ST2GeneProductENSG00000171004 (Ensembl)
HS6ST3GeneProductENSG00000185352 (Ensembl)
Heparan-Glc-N-3-6-trisulfateMetaboliteMetaNetX: MNXM18334
Heparan-GlcN-6-N-bisulfateMetaboliteMetaNetX: MNXM11794
Heparan-sulfate-3-N-disulfateMetaboliteMetaNetX: MNXM8703
Heparan-sulfate-L-IdoA-2SMetaboliteMetaNetX: MNXM96199
NDST1GeneProductENSG00000070614 (Ensembl)
NDST2GeneProductENSG00000166507 (Ensembl)
NDST3GeneProductENSG00000164100 (Ensembl)
NDST4GeneProductENSG00000138653 (Ensembl)
UDP-N-acetyl-α-D-galactosamineMetabolite67138 (ChEBI)
UDP-α-D-galactoseMetabolite66914 (ChEBI)
UDP-α-D-glucuronateMetabolite58052 (ChEBI)
UDP-α-D-xyloseMetabolite57632 (ChEBI)
USTGeneProductENSG00000111962 (Ensembl)
XYLT1GeneProductENSG00000103489 (Ensembl)
XYLT2GeneProductENSG00000015532 (Ensembl)
[heparan sulfate] containing GlcNSMetabolite13555 (ChEBI)
[heparosan]-containing α-L-iduronateMetabolite17174 (ChEBI)
chondroitin 4'-sulfateMetabolite18250 (ChEBI)
chondroitin 6'-sulfateMetabolite18296 (ChEBI)
chondroitin-[core protein]Metabolite16137 (ChEBI)
deacetylated heparosan-[core protein]MetaboliteC02834 (KEGG Compound)
dermatan-[core protein]Metabolite4439 (ChEBI)
heparin-glucosamine-3-O-sulfateMetaboliteC04072 (KEGG Compound)
heparosan-[core protein]Metabolite24500 (ChEBI)

Annotated Interactions

No annotated interactions

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